Crowder T L, Ariwodola O J, Weiner J L
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
J Pharmacol Exp Ther. 2002 Dec;303(3):937-44. doi: 10.1124/jpet.102.038471.
Many studies have demonstrated that ethanol reduces glutamatergic synaptic transmission primarily by inhibiting the N-methyl-D-aspartate subtype of glutamate receptor. In contrast, the other two subtypes of ionotropic glutamate receptor (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid and kainate) have generally been shown to be insensitive to intoxicating concentrations of ethanol. However, we have previously identified a population of kainate receptors that mediate slow excitatory postsynaptic currents in the rat hippocampal CA3 pyramidal cell region that is potently inhibited by low concentrations of ethanol. In this study, we examined the effect of ethanol on kainate receptor-mediated inhibition of evoked GABA(A) inhibitory postsynaptic currents (IPSCs) in the rat hippocampal CA1 pyramidal cell region. Under our recording conditions, bath application of 1 microM kainate significantly inhibited GABA(A) IPSCs. This inhibition seemed to be mediated by the activation of somatodendritic kainate receptors on GABAergic interneurons and the subsequent activation of metabotropic GABA(B) receptors, because the kainate inhibition was largely blocked by pretreating slices with a GABA(B) receptor antagonist. Ethanol pretreatment significantly antagonized the inhibitory effect of kainate on GABA(A) IPSCs, at concentrations as low as 20 mM. In contrast, ethanol did not block the direct inhibitory effect of a GABA(B) receptor agonist on GABA(A) IPSCs. The results of this study suggest that modest concentrations of ethanol may antagonize presynaptic, as well as postsynaptic, kainate receptor function in the rat hippocampus.
许多研究表明，乙醇主要通过抑制谷氨酸受体的N-甲基-D-天冬氨酸亚型来降低谷氨酸能突触传递。相比之下，离子型谷氨酸受体的其他两种亚型（α-氨基-3-羟基-5-甲基异恶唑-4-丙酸和海人酸）通常被证明对中毒浓度的乙醇不敏感。然而，我们之前已经鉴定出一群海人酸受体，它们在大鼠海马CA3锥体细胞区域介导缓慢的兴奋性突触后电流，这种电流会被低浓度乙醇强烈抑制。在本研究中，我们检测了乙醇对大鼠海马CA1锥体细胞区域中海人酸受体介导的诱发GABA(A)抑制性突触后电流（IPSCs）的影响。在我们的记录条件下，浴槽中加入1微摩尔的海人酸可显著抑制GABA(A) IPSCs。这种抑制似乎是由GABA能中间神经元上树突体海人酸受体的激活以及随后代谢型GABA(B)受体的激活介导的，因为在用GABA(B)受体拮抗剂预处理切片后，海人酸的抑制作用大部分被阻断。乙醇预处理在低至20毫摩尔的浓度下就能显著拮抗海人酸对GABA(A) IPSCs的抑制作用。相比之下，乙醇并不阻断GABA(B)受体激动剂对GABA(A) IPSCs的直接抑制作用。本研究结果表明，适度浓度的乙醇可能会拮抗大鼠海马中突触前和突触后海人酸受体的功能。
